Metabolism and activation of aflatoxin B1 by reconstituted cytochrome P-450 system of rat liver.
Metabolism and activation of aflatoxin B1, a potent hepatocarcinogenic and mutagenic mycotoxin of Aspergillus flavus, were investigated in the reconstituted enzyme system composed of purified NADPH-cytochrome P-450 reductase and cytochrome P-450 or P-448 of rat liver. The aflatoxin M1 formation was strictly mediated by P-448 purified from the liver microsomes of polychlorobiphenyl- and 3-methylcholanthrene-treated rats, while the aflatoxin Q1 formation, as well as the binding of DNA, were catalyzed by both P-450 and P448. Differences between the kinetic data on metabolism and activation of aflatoxin B1 obtained with the reconstituted cytochrome systems and those obtained with the microsomal and nuclear systems were discussed, and the significance of these biochemical data in the in vivo carcinogenicity of aflatoxin B1 was evaluated.
D016604:Aflatoxin B1; D016607:Aflatoxin M1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002467:Cell Nucleus / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital; D011078:Polychlorinated Biphenyls; D051381:Rats
D000348:Aflatoxins; C033759:aflatoxin Q1; D008748:Methylcholanthrene; D016607:Aflatoxin M1; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D011078:Polychlorinated Biphenyls; D010634:Phenobarbital